Several investigators have reported that plasmapheresis may be of benefit in patients with multiple sclerosis (MS) both those with acute exacerbations and those with chronic progressive disease. nder the auspices of the National Multiple Sclerosis Society, a working committee of investigators was formed to design a clinical trial which would definitively establish whether plasmapheresis has a role in the treatment of MS. This proposal represents the recommendations of that group. It was decided that plasmapheresis would be of most benefit in patients with acute exacerbations and that a double-blind study which included "control pheresis" (i.e., being hooked-up to the machine without removal of plasma) was the best study design and was feasible to perform. 150 patients will be studied in 5 centers over a 2-3 year period. One group will receive ACTH, oral immunosuppression with cyclophosphamide, and 11 pheresis over an 8 week period. The second group will receive identical treatment except for "control pheresis." The patients to be studied will be defined in an identical way to those studied in the cooperative study of ACTH in acute MS performed in the 1960's. The follow-up period after treatment will be one year, at which time final clinical evaluation will be performed and the two groups compared. Biostatistical analysis will be performed at study headquarters utilizing standardized reporting and clinical evaluation forms. The goal of the study is to determine, not only if pheresis affects recovery from acute attacks but whether there is a difference between the two patient groups one year following treatment.